Composition containing an extract from muirapuama root and plant worm extract

ABSTRACT

PCT No. PCT/JP96/03733 Sec. 371 Date Jun. 4, 1998 Sec. 102(e) Date Jun. 4, 1998 PCT Filed Dec. 20, 1996 PCT Pub. No. WO97/24134 PCT Pub. Date Jul. 10, 1997A composition containing natural drugs is disclosed. The composition is effective for relieving physical and mental fatigue and for ameliorating a weakened constitution without any side effects, even if administered for a long time.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a composition directed to relievingphysical and mental fatigue and also to ameliorating or restoring aweakened constitution, etc., which comprises muirapuama and plant worms.

2. Description of the Related Art

Muirapuama is a natural drug used in the Amazon river basin in the olddays as an invigorating or restoring tonic. Plant worms are also anatural drug used in China in the old days as a sedative or anantitussive.

Orally administering compositions containing a muirapuama extract or anextract of plant worms alone as an effective ingredient are known, but acomposition containing both muirapuama and plant worms together is notyet disclosed.

Dialog Information Service, File 377, Derwent Drug File, DialogAccession No. 00510368, Derwent Accession No. 92-51335 describes the useof a composition comprising muirapuama for the treatment of physical andmental fatigue.

An object of the present invention is to provide a composition havingthe intensified restoring effect of muirapuamna on depressed physicalstrength or stamina due to stress by combining with plant worms; havingthe effect of relieving stress and physical fatigue; and having theeffect of ameliorating or restoring a weakened constitution without anyside effects, even if administered for a long time.

SUMMARY OF THE INVENTION

As a result of extensive studies, the present inventors have found anovel combination of muirapuama with plant worms, which has asynergistic effect on relieving physical and mental fatigue due tostress, and ameliorating a weakened constitution, where muirapuama caneffectively normalize stress, that is, disturbances in bodies due tovarious external and internal factors and plant worms can effectivelypromote metabolism and relieve physical and mental fatigue such as ageneral feeling of weariness, drowsiness, and a feeling of expansion.

According to the present invention, there is provided a compositioncomprising muirapuama and plant worms as effect ingredients forrelieving physical and mental fatigue, stress, and ameliorating aweakened constitution or recovery therefrom, without any side effects,even if administered for a long time.

Original plants for muirapuama for use in the present invention areshrubs of family Olacaceae growing in the Amazon river basin in Brazil,including such species as Ptychopetalum olacoides, Ptychopetlumuncinatum, and Liriosma ovata, among which, the species Ptychopetalumolacoides is preferable. Needless to say, the species Ptychopetlumuncinatum and Liriosma ovata can also be used. In the present invention,roots of these original plants are used.

Plant worms are stomas of preferably the genus Cordyceps of familyClavicipitaceae and larvas of insects on which the genus Cordyceps areparasitic. Those of genuses Simizuomyces, Podonectrioides, andTorrbiella of the same family Clavicipitaceae can be also used.

The muirapuama of the present invention can be used as an extract andthe extract can be obtained in the following manner:

Finely shredded muirapuama roots are mixed with dilute ethanol andsubjected to infusion for 2 days with occasional stirring, and theresulting infusion is filtered. The residues are further mixed withdilute ethanol and subjected to infusion for 2 days with occasionalstirring and the resulting infusion is also filtered. The resulting twofiltrates are combined together and concentrated under reduced pressureto obtain a muirapuama extract.

The plant worms of the present invention can be used as an extract or afluid extract and the extracts can be obtained in the following manner:

Rough-shredded plant worms are mixed with dilute ethanol and leftstanding at room temperature for about 2 hours, and then the resultingsolution is further mixed with dilute ethanol and subjected to infusionby leaving the solution standing at room temperature for 3 days toobtain an extract as an infusion. The thus obtained extract is leftstanding at room temperature for 2 days and filtered through a filterpaper to obtain a fluid extract.

According to the present invention, the effective dosage of muirapuamaextract, for an adult is 10 to 5,000 mg/day, preferably 50 to 1,500mg/day in terms of bulk natural drug, and the effective dosage of fluidextract of plant worms for an adult is 10 to 5,000 mg/day, preferably 50to 1,000 mg/day in terms of bulk natural drug. That is, 0.002 to 500parts by weight, preferably 0.03 to 30 parts by weight, more preferably0.5 to 8 parts by weight, of a muirapuama extract is used per part byweight of a fluid extract of plant worms in terms of bulk natural drugs.

The present composition can contain caffeine; water-soluble vitamins,such as vitamin B₁, vitamin B₂, vitamin B₆, vitamin B₁₂, vitamin C,biotin, carnitine, pantotenic acid, and nicotinic acid and theirderivatives; fat soluble vitamins, such as vitamin A, vitamin E andtheir derivatives; taurine; amino acids, such as arginine; and othernatural drugs, such as extracts or tinctures of agkistrodon, ginseng,astragalus root, polygonati root, licorice, poria sclerotium, rehmanniaroot, Japanese angelica root, lycii fruit, cinnamon bark, velvet horm,barren-worts, cistanchis caulis, Chinese gutta percha, schisandra fruit,eleutherococc, ophiopogon tuber, polygoni multiflori root, and bovinebile.

The present composition can be administered or taken directly as is, oras medical preparations, for example, preparations for oraladministration (e.g., granules, powder, capsules, tablets, dry syrup,liquid preparations) or injection, or foods, for example, soft drinks orsolid foods (e.g., biscuits), prepared by mixing with other knownadditives, for example, a vehicle, a disintegrator, a binder, alubricant, an antioxidant, a coating agent, a coloring agent, acorrigent, a surfactant, a plasticizer, a pH regulating agent, arefreshing agent, a suspending agent, a defoaming agent, a thickeningagent, a dissolving aid, etc., according to ordinary methods or can beadded to soft drinks or food as a functional ingredient or an additive.

According to the present invention, a single composition of a muirapuamaextract and a single composition of an extract of plant worms can besealed in separate ampules, respectively, and used upon mixing of thesingle composition or used without the simultaneously mixing whenadministered.

The vehicle includes, for example, a sugar alcohol such as D-mannitol,xylitol and D-sorbitol; saccharides such as glucose, sucrose, lactoseand fruit sugar, crystalline cellulose, sodium carmellose, calciumhydrogen phosphate, wheat starch, rice starch, corn starch, potatostarch, dextrin, β-cyclodextrin, light anhydrous silicic acid, titaniumoxide, and magnesium metasilicate aluminate.

The disintegrator includes, for example, low-substituted hydroxypropylcellulose, calcium carboxymethyl cellulose, sodium croscarmellosehydroxypropyl starch, and partially gelatinized starch.

The binder includes, for example, methyl cellulose, hydroxypropylcellulose, hydroxypropylmethyl cellulose, polyvinylpyrrolidone, gelatin,gum arabic, ethyl cellulose, polyvinyl alcohol, pullulan, gelatinizedstarch, agar, tragacanth, sodium alginate, and propylene glycolalginate.

The lubricant includes, for example, stearic acid, magnesium stearate,calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil,sucrose fatty acid ester, dimethylpolysiloxane, yellow beeswax, andwhite beeswax.

The antioxidant includes, for example, dibutylhydroxytoluene (BHT),propyl gallate, butylhydroxyanisole (BHA), tocopherol, and citric acid.

The coating agent includes, for example, hydroxypropylmethyl cellulose,hydroxypropyl cellulose, methyl cellulose, ethyl cellulose,hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl celluloseacetate succinate, carboxymethylethyl cellulose, cellulose acetatephthalate, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylatecopolymer, hydroxypropylmethyl cellulose acetate succinate, methacrylicacid copolymer, polyvinyl acetate diethylaminoacetate, and shellac.

The coloring agent includes, for example, a turmeric extract,riboflavin, carotin solution, and titanium oxide.

The surfactant includes, for example, polyoxyethylene hydrogenatedcastor oil, glycerin monostearate, sorbitan monostearate, sorbitanmonolaurate, polyoxyethylene polyoxypropylene, polysolvates, sodiumlaurylsulfate, macrogols, and sucrose fatty acid ester.

The plasticizer includes, for example, triethyl citrate, polyethyleneglycol, triacetin, and cetanol.

The pH regulating agent includes, for example, citric acid, malic acid,sodium hydrogen phosphate, and dipotassium hydrogen phosphate.

The refreshing agent includes, for example, 1-menthol and mentha water.

The suspending agent includes, for example, kaolin, sodium carmellose,xanthane gum, and tragacanth.

The defoaming agent includes, for example, dimethyl polysiloxane andsilicone deforming agent.

The thickening agent includes, for example, xanthane gum, tragacanth,methyl cellulose, and dextrin.

The dissolving aid includes, for example, ethanol, sucrose fatty acidester, and macrogol.

In case of soft drinks, a particularly desired taste or flavor can beobtained by adding other physiologically active substances, minerals,vitamins, hormones, nutrients, and/or flavorings, to the presentcomposition, in addition to the above-mentioned additives.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows durable swimming time of rats in forced swimming byadministration of the present liquid preparation (plant worms andmuirapuama), a single liquid preparation of plant worms, and muirapuama,respectively, and a control (purified water).

FIG. 2 shows total intakes of the present liquid preparation (plantworms and muirapuama), a single liquid preparation of plant worms andmuirapuama, respectively, and a control (purified water) by exercisegroups and non-exercise group.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will be described in detail below, referring toExamples and Test Examples, and drawings.

EXAMPLE

    ______________________________________                                        Formulation                                                                   ______________________________________                                        Plant worms         100 mg (in terms of                                                          bulk natural drug)                                         Muirapuama          300 mg (in terms of                                                          bulk natural drug)                                         Agkistrodon         250 mg (in terms of                                                          bulk natural drug)                                         Taurine             500 mg                                                    Ginseng             600 mg (in terms of                                                          bulk natural drug)                                         Astragalus          300 mg (in terms of                                                          bulk natural drug)                                         Polygonati root     300 mg (in terms of                                                          bulk natural drug)                                         Licorice root       150 mg (in terms of                                                          bulk natural drug)                                         Poria sclerotium    300 mg (in terms of                                                          bulk natural drug)                                         Rehmannia root      200 mg (in terms of                                                          bulk natural drug)                                         Japanese angelica root                                                                            200 mg (in terms of                                                          bulk natural drug)                                         Lycii fruit         200 mg (in terms of                                                          bulk natural drug)                                         Cinnamon bark       150 mg (in terms of                                                          bulk natural drug)                                         Velvet horn         300 mg (in terms of                                                          bulk natural drug)                                         Barren-worts       1000 mg (in terms of                                                          bulk natural drug)                                         Vitamin B.sub.2      5 mg                                                     Vitamin B.sub.6      5 mg                                                     Anhydrous caffeine  50 mg                                                     ______________________________________                                    

The foregoing components were further mixed with appropriate amounts ofsodium citrate, malic acid, sucrose, D-sorbitol solution, benzoic acid,polyoxyethylene hydrogenated castor oil and distilled water to make 50ml of liquid preparation.

EXAMPLE

    ______________________________________                                        Formulation                                                                   ______________________________________                                        Plant worms         150 mg (in terms of                                                          bulk natural drug)                                         Muirapuama          350 mg (in terms of                                                          bulk natural drug)                                         Agkistrodon         300 mg (in terms of                                                          bulk natural drug)                                         Taurine             500 mg                                                    Ginseng             600 mg (in terms of                                                          bulk natural drug)                                         Astragalus root     300 mg (in terms of                                                          bulk natural drug)                                         Polygonati root     300 mg (in terms of                                                          bulk natural drug)                                         Licorice            150 mg (in terms of                                                          bulk natural drug)                                         Poria sclerotium    300 mg (in terms of                                                          bulk natural drug)                                         Rehmannia root      200 mg (in terms of                                                          bulk natural drug)                                         Japanese angelica root                                                                            200 mg (in terms of                                                          bulk natural drug)                                         Lycii fruit         200 mg (in terms of                                                          bulk natural drug)                                         Cinnamon bark       150 mg (in terms of                                                          bulk natural drug)                                         Velvet horn         300 mg (in terms of                                                          bulk natural drug)                                         Barren-worts       1000 mg (in terms of                                                          bulk natural drug)                                         Vitamin B.sub.2      5 mg                                                     Vitamin B.sub.6      5 mg                                                     Anhydrous caffeine  50 mg                                                     ______________________________________                                    

The foregoing components were further mixed with appropriate amounts ofcitric acid, sodium citrate, sucrose, D-sorbitol solution, benzoic acid,polyoxyethylene hydrogenated castor oil and distilled water to make 50ml of liquid preparation.

EXAMPLE

    ______________________________________                                        Formulation                                                                   ______________________________________                                        Plant worms         300 mg (in terms of                                                          bulk natural drug)                                         Muirapuama          300 mg (in terms of                                                          bulk natural drug)                                         Agkistrodon         250 mg (in terms of                                                          bulk natural drug)                                         Taurine             500 mg                                                    Ginseng             600 mg (in terms of                                                          bulk natural drug)                                         Astragalus root     300 mg (in terms of                                                          bulk natural drug)                                         Licorice root       100 mg (in terms of                                                          bulk natural drug)                                         Poria sclerotium    250 mg (in terms of                                                          bulk natural drug)                                         Rehmannia root      300 mg (in terms of                                                          bulk natural drug)                                         Japanese angelica root                                                                            300 mg (in terms of                                                          bulk natural drug)                                         Cistanchis caulis   300 mg (in terms of                                                          bulk natural drug)                                         Chinese gutta percha                                                                              300 mg (in terms of                                                          bulk natural drug)                                         Schisandra fruit    200 mg (in terms of                                                          bulk natural drug)                                         Cinnamon bark       200 mg (in terms of                                                          bulk natural drug)                                         Velvet horn         300 mg (in terms of                                                          bulk natural drug)                                         Barren-worts       1000 mg (in terms of                                                          bulk natural drug)                                         Vitamin B.sub.2      5 mg                                                     Vitamin B.sub.6      5 mg                                                     Anhydrous caffeine  50 mg                                                     ______________________________________                                    

The foregoing components were further mixed with appropriate amounts ofcitric acid, sodium citrate, sucrose, D-sorbitol solution, benzoic acid,polyoxyethylene hydrogenated oil and distilled water to make 50 ml ofliquid preparation.

EXAMPLE

    ______________________________________                                        Formulation                                                                   ______________________________________                                        Plant worms         330 mg (in terms of                                                          bulk natural drug)                                         Muirapuama          450 mg (in terms of                                                          bulk natural drug)                                         Agkistrodon         400 mg (in terms of                                                          bulk natural drug)                                         Taurine             500 mg                                                    Ginseng             600 mg (in terms of                                                          bulk natural drug)                                         Astragalus root     300 mg (in terms of                                                          bulk natural drug)                                         Licorice root       100 mg (in terms of                                                          bulk natural drug)                                         Poria sclerotium    250 mg (in terms of                                                          bulk natural drug)                                         Rehmannia root      300 mg (in terms of                                                          bulk natural drug)                                         Japanese angelica root                                                                            300 mg (in terms of                                                          bulk natural drug)                                         Cistanchis caulis   300 mg (in terms of                                                          bulk natural drug)                                         Chinese gutta percha                                                                              300 mg (in terms of                                                          bulk natural drug)                                         Schisandra fruit    200 mg (in terms of                                                          bulk natural drug)                                         Cinnamon bark       200 mg (in terms of                                                          bulk natural drug)                                         Velvet horn         300 mg (in terms of                                                          bulk natural drug)                                         Barren-worts       1000 mg (in terms of                                                          bulk natural drug)                                         Vitamin B.sub.2      5 mg                                                     Vitamin B.sub.6      5 mg                                                     Anydrous caffeine   50 mg                                                     ______________________________________                                    

The foregoing components were further mixed with appropriate amounts ofsodium citrate, malic acid, sucrose, D-sorbitol solution, benzoic acid,polyoxyethylene hydrogenated oil and distilled water to make 50 ml ofliquid preparation.

EXAMPLE

    ______________________________________                                        Formulation                                                                   ______________________________________                                        Plant worms          100 mg (in terms of                                                          bulk natural drug)                                        Muirapuama           300 mg (in terms of                                                          bulk natural drug)                                        Rehmannia root      1500 mg (in terms of                                                          bulk natural drug)                                        Barren-worts         500 mg (in terms of                                                          bulk natural drug)                                        Eleutherococc        750 mg (in terms of                                                          bulk natural drug)                                        Polygonati root      750 mg (in terms of                                                          bulk natural drug)                                        Velvet horn          250 mg (in terms of                                                          bulk natural drug)                                        Ginseng             3000 mg (in terms of                                                          bulk natural drug)                                        Ophiopogon tuber    1200 mg (in terms of                                                          bulk natural drug)                                        Schisandra fruit     500 mg (in terms of                                                          bulk natural drug)                                        Polygoni multiflori root                                                                           750 mg (in terms of                                                          bulk natural drug)                                        Cinnamon bark        500 mg (in terms of                                                          bulk natural drug)                                        ______________________________________                                    

The foregoing components were uniformly mixed with appropriate amountsof mannitol, hydroxypropyl cellulose, magnesium metasilicate aluminate,aspartame and flavoring and made into three packages of granules.

EXAMPLE

    ______________________________________                                        Formulation                                                                   ______________________________________                                        Plant worms         300 mg (in terms of                                                          bulk natural drug)                                         Muirapuama          300 mg (in terms of                                                          bulk natural drug)                                         Rehmannia root     1000 mg (in terms of                                                          bulk natural drug)                                         Polygonati root     500 mg (in terms of                                                          bulk natural drug)                                         Velvet horn         250 mg (in tenns of                                                          bulk natural drug)                                         Ginseng            2000 mg (in terms of                                                          bulk natural drug)                                         Vitamin B.sub.2     10 mg                                                     Vitamin B.sub.6      5 mg                                                     ______________________________________                                    

The foregoing components were uniformly mixed with appropriate amountsof magnesium mctasilicate aluminate, polysolvate 60 and propyleneglycol, and the resulting mixture was uniformly filled into softcapsules to obtain 9 capsules of preparate.

EXAMPLE

    ______________________________________                                        Formulation                                                                   ______________________________________                                        Plant worms           100 mg (in terms of                                                          bulk natural drug)                                       Muirapuama            200 mg (in terms of                                                          bulk natural drug)                                       Barren-worts          500 mg (in terms of                                                          bulk natural drug)                                       Velvet horn           200 mg (in terms of                                                          bulk natural drug)                                       Ginseng               600 mg (in terms of                                                          bulk natural drug)                                       Polygonium multiflori root                                                                          300 mg (in terms of                                                          bulk natural drug)                                       Bovine bile           650 mg (in terms of                                                          bulk natural drug)                                       L-arginine hydrochloride                                                                            100 mg                                                  dl-carnitine chloride                                                                               50 mg                                                   Vitamin A            2000 I.U.                                                Vitamin B.sub.1       20 mg                                                   Vitamin B.sub.2       15 mg                                                   Vitamin B.sub.6        5 mg                                                   Vitamin B.sub.12      10 μg                                                Nicotinic acid amide  20 mg                                                   Calcium pantothenate  30 mg                                                   Vitamin C             50 mg                                                   Vitamin E              5 mg                                                   ______________________________________                                    

The foregoing components were uniformly mixed with appropriate amountsof sodium hydrogen carbonate, polyvinyl pyrrolidone, light anhydroussilicic acid, magnesium stearate, polyethylene glycol, polysolvate 80and flavoring to obtain 9 tablets of preparate.

TEST EXAMPLE 1

The following groups, each consisting of 7 male SD rats having anaverage body weight of 200 g, were tested by orally administeringpredetermined equal volumes of the following liquid preparations andsubjecting the rats to forced swimming to determine durable swimmingtime.

Group A: administered with the present liquid preparation (plant worms :0.2 w/v %+muirapuama: 0.6 w/v % in terms of bulk natural drugs)

Group B: administered with a single liquid preparation of plant worms(0.8 w/v % in terms of bulk natural drug)

Group C: administered with a single liquid preparation of muirapuama(0.8 w/v % in terms of bulk natural drug)

Group D: control (only purified water)

Results of durable swimming time of groups A, B, C and D are shown inFIG. 1.

As is evident from FIG. 1, the durable swimming time is much moreextended in the case of Group A with the present liquid preparation thanthose in the cases of Groups B and C with the single liquidpreparations.

TEST EXAMPLE 2

Male SD rats having an average body weight of 200 g were divided intothe following exercise groups each consisting of 5 rats and non-exercisegroups each consisting of 7 rats, and the exercise groups were subjectedto forced swimming tests by conducting forced swimming for 30 minutesper day for a total 10 days while applying about 10% weight load perbody weight to the respective rats, and by carrying out a two-bottleselective test with the following liquid preparations from the first dayuntil the 10th day from the application of forced swimming load todetermine their total intakes. The non-exercise groups were also testedin the same manner as above without any application of forced swimmingunder the weight load.

Group A: intake of the present liquid preparation (plant worms: 0.2 w/v%+muirapuama: 0.6 w/v % in terms of bulk natural drugs)

Group B: intake of a single liquid preparation of plant worms (0.8 w/v %in terms of original natural drug)

Group C: intake of a single liquid preparation of muirapuama (0.8 w/v %in terms of bulk natural drug)

Group D: control (intake of purified water)

The total intakes of the exercise groups and the non-exercise groupswere compared, and the results are shown in FIG. 2.

As is evident from FIG. 2, the total intake of the present liquidpreparation A by the exercise group is drastically increased, ascompared with the total intakes of the single liquid preparations B andC by the exercise groups.

What is claimed is:
 1. A composition comprising about 0.5 to 8 parts byweight muirapuama in an organic solvent extract from amuirapuama-containing root of shrubs of the family Olacaceae and about 1part by weight of plant worm active ingredient in an organic solventextract from at least one plant worm of the family Clavicipitaceae.